The liver from human stem cells started working in the mouse body

A mouse grows a human liver

Polina Rozentsvet, Newspaper.Roo

Japanese scientists have constructed a rudimentary liver from human stem cells and transplanted it into a mouse organism, where the transplant grows and successfully performs the functions of a mature organ.

The main obstacle to transplantation is not the complexity of the operation, but the acute shortage of suitable donors. It is not surprising that since 1981, specialists in different countries have been making efforts to obtain artificial organs: they design them on a frame, grow them in miniature and even try to print them on a 3D printer.

Specialists from the University of Yokohama and several Japanese clinics under the guidance of Professor Hideki Taneguchi experimented with artificial liver. They abandoned the idea of growing a full-sized organ and created its rudiment, similar to that formed during the natural embryonic development of the liver. They transplanted such an embryo into the mouse's body, where it successfully grew and functioned as a full-fledged organ.

The scientists published an article about the results of their work on July 4 in the journal Nature (Takebe et al., Vascularized and functional human liver from an iPSC-derived organ bud transplant).

The liver is formed from a lump of cells, which is isolated from the intestinal tube of the fetus at the 3rd-4th week of development. In order for this rudiment to turn into a full-fledged organ, it is necessary to coordinate the action of many signaling molecules secreted by cells of other germ layers. The researchers tried to grow such an embryo in a Petri dish with a nutrient medium. They used human pluripotent stem cells, that is, those that, with proper exposure, can turn into mature cells of different tissues. In this case, their development was directed in such a way that they differentiated into precursors of liver cells. Cells from other germ layers, which are involved in the formation of the liver in a living organism, were planted in the nutrient medium to them.

Within 48 hours, the cell layer self–organized into a compact three-dimensional structure - an artificial rudiment of the liver. It is stable and can be manipulated. Its cells divide and synthesize the same proteins as the cells of the human fetal liver germ. But can this lump become a full-fledged organ, that is, grow into vessels?

Scientists transplanted such rudiments of the human liver to mice. Photograph: Takanori Takebe

To find out, the researchers placed the rudiment of the liver in the body of immunodeficient mice, in a place where it is convenient to observe its development. Mice with weakened immune systems did not reject the graft. Within 48 hours, blood vessels formed in it, which connected with the host's circulatory system. The density of the vascular network was about the same as in an adult liver. The formation of blood vessels and, consequently, normal blood supply stimulated the maturation of the organ. The rudimentary liver developed in the mouse body for two months, gradually acquiring the structure of a mature liver and synthesizing proteins characteristic of it.

One of the functions of the liver is detoxification, it breaks down chemicals that are not harmless components. Mice were injected with two drugs, ketoprofen and debrisoquin, which decompose differently in the human and mouse liver.

In the urine and blood serum of rodents, researchers found the products of drug cleavage, but these are the products that are formed in the human liver. This indicates that the human liver has started working in the mouse body.

When the mouse liver was destroyed by ganciclovir, the transplanted human liver saved them from liver failure and imminent death. A small transplant copes with its tasks like a real liver.

The researchers believe that they have demonstrated a high therapeutic potential of organ embryos grown from stem cells. There is still a lot of effort to be made to adapt this technology for humans, but scientists hope that sooner or later regenerative medicine will replace the transplantation of donor organs.

Portal "Eternal youth" http://vechnayamolodost.ru04.07.2013